CHAPTER 4. Discussion and Conclusion
4.1. DIscussion
existing diagnosis of hypertension at baseline presentation with heart failure. Despite the frequency of pre-existing hypertension, the vast majority of patients had no additional co- morbidities. Although infrequent, diabetes, chronic renal disease and HIV were the most common co-morbidities seen in our cohort, and an increase in the number of co-morbidities appears to be a risk factor for premature death. Although difficult to interpret in the setting of congestive heart failure, the majority of patients in this cohort were overweight, an observation that was not significantly altered by the resolution of congestion at follow-up, and has been as described in other South African studies on hypertension.18,71 Although infrequent, anaemia was seen in a few patients, particularly in the postpartum period. As iron deficiency and anaemia are associated with worse clinical outcomes72 and may be a precipitant for decompensated heart failure, addressing anaemia and iron deficiency in patients with hypertension, in addition to blood pressure control, may help to mitigate subsequent decompensation. Contrary to what has been reported in other cohorts50 atrial fibrillation was an infrequent finding at baseline or at follow-up in this group of patients.
The diagnosis of HHD in the context of impaired systolic function is challenging, and blood pressure readings at baseline may not accurately reflect underlying hypertension. Pseudo- normal readings in the context of HFrEF may be attributed to decreased cardiac output and the effects of therapy, including hypovolemia secondary to loop diuretic use and vasodilation.73 Of note, there may be differences in BP readings based on the presentation of heart failure. It has been shown that that patients that present with acute decompensated chronic heart failure are usually able to maintain their blood pressure based on the compensatory mechanisms.
New onset acute heart failure does not produce the appropriate feedback mechanisms to preserve the blood pressure.74 In our study, mean systolic blood pressure at baseline presentation with heart failure was only marginally elevated, and ranged from 88 to 172 mmHg. Despite the variation in blood pressure measurements at baseline, the presence of hypertension and/or TOD was confirmed in all patients during follow-up, indicating that the
is a linear association between raised blood pressure and cardiovascular disease75, lower blood pressures in the context of HFrEF may not necessarily reflect reduced risk. There are no clear guidelines on BP targets for patients with HHD and heart failure.9 Optimization of therapy in HHD with HFrEF or HFmrEF is currently based of general heart failure guidelines, and is not tailored specifically to blood pressure targets. This may be relevant in patients that present with elevated blood pressures and heart failure, and in those patients that recover their LV function on anti-failure therapy with subsequent unmasking of underlying hypertension.
The detection of LVH was not a prominent finding across this cohort; less than a third of patients had LVH on echocardiogram and the median wall thickness across the cohort was within the normal range. This challenges traditional definitions for HHD where LVH has been included as an important criteria.25 In contrast to dilated cardiomyopathy where wall thinning is frequently observed (Kraus, S. 2019. Ph.D. Thesis. UCT), LV wall thickness may be normal or, less frequently, increased in HHD. Regression of LVH in patients with hypertension is associated with a reduction of target organ damage associated with hypertension.76 The pseudo-normalisation of blood pressure in HHD with HFrEF, in conjunction with other factors such as younger age and lack of co-morbidities, may possibly account for lower rates of LVH and target organ damage in our cohort, although this has not been proven in this study. The degree of target organ damage is difficult to accurately report as fundoscopy, urine dipstick and urine protein creatinine ratios were not done (or not recorded) in the vast majority of patients at clinic visits. Routine evaluation of the non-cardiac TOD should be conducted in all patients with heart failure secondary to HHD, regardless of blood pressure readings. Urine protein:creatinine ratio may also be helpful in distinguishing between hypertensive renal disease (TOD) or primary chronic kidney disease, and cardiorenal syndrome in patients with HHD and heart failure. Although renal dysfunction was seen in less than a fifth of patients at presentation, univariate and multivariate logistical regression analysis indicates that an abnormal baseline creatinine is associated with lower rates of complete recovery at follow-up.
Most patients were initiated on appropriate therapy for HF but were on suboptimal doses at baseline. The proportion of patients on optimal drug doses for heart failure did increase substantially over the follow-up period, however, 24% and 37% of patients were still on sub- optimal doses of ACE-inhibitors and beta-blockers at the second follow-up (13.2 [IQR 9.1- 15.7] months). Despite this, the rate of mortality or transplantation was low for a heart failure cohort and a significant number of patients had partial or complete recovery of their LVEF.
Ideally, the ACE-I should have been up-titrated to optimal doses prior to the addition of calcium channel blockers as this has no effect on mortality or survival. Studies have shown that ACE- I and beta blockers improve left ventricular volume, hypertrophy and LVEF.77-79 Reverse remodeling, specifically regression of LVH and improvement of left ventricular dimensions and LVEF, has a proven positive outcome on mortality,80 therefore, optimisation of heart failure therapy would likely improve outcomes and recovery rates even further. Transplant-free survival was surprisingly good (98.3% and 90.5% at 1- and 3-years, respectively), in comparison to outcomes reported in heart failure studies conducted in Sub-Saharan Africa, despite hypertension being identified as the leading cause for heart failure in these cohorts.1,8,81 Overall survival was good in this cohort although there was no statistically significant survival difference between HFrEF and HFmrEF.
It is not yet fully known what causes a particular subset of patients with hypertension develop HHD with HFrEF, nor why the cardiac insult appears to be so severe compared to other organ involvement. Contributing factors, such as increased alcohol intake, pregnancy, co-morbidities such as Diabetes Mellitus and HIV, and genetic predisposition, may possibly render the myocardium more vulnerable and further research is necessary to better understand the relationship between hypertension and these factors.